Soares-da-Silva P
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Biochem Pharmacol. 1992 Nov 3;44(9):1883-6. doi: 10.1016/0006-2952(92)90085-w.
The present study has examined the effect of colchicine and cytochalasin B, two cytoskeleton disrupter compounds, on the formation of dopamine in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA); the deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) was also examined. The accumulation of newly formed dopamine and DOPAC in kidney slices loaded with L-DOPA (10-100 microM) was found to be dependent on the concentration of L-DOPA, being similar in control conditions and in preparations treated with increasing concentrations of colchicine (5, 10 and 50 microM). By contrast, cytochalasin B (5, 10 and 50 microM) was found to produce a concentration-dependent reduction in the formation of dopamine and of its deaminated metabolite DOPAC in kidney slices loaded with L-DOPA (10-100 microM). The inhibitory effect of cytochalasin B on the formation of dopamine was found to be completely abolished in kidney slices pretreated with ouabain (500 microM) or when sodium concentration in the incubation was reduced from 120 to 20 mM. On its own, ouabain (500 microM) was found to reduce the formation of dopamine by 55%; the effect of reducing sodium concentration in the incubation medium to 20 mM was also a significant reduction (53% decrease) in the formation of dopamine. The accumulation of DOPAC did always parallel that of its parent amine. It is concluded that the renal formation of dopamine is dependent on the concentration of sodium in the medium and the integrity of the tubular transport of sodium, namely on the association between actin cytoskeleton and Na+,K(+)-ATPase, appears to be determinant.
本研究检测了两种细胞骨架破坏化合物秋水仙碱和细胞松弛素B对加载外源性L-3,4-二羟基苯丙氨酸（L-DOPA）的大鼠肾皮质切片中多巴胺形成的影响；还检测了新形成的多巴胺脱氨生成3,4-二羟基苯乙酸（DOPAC）的情况。发现加载L-DOPA（10 - 100微摩尔）的肾切片中新形成的多巴胺和DOPAC的积累取决于L-DOPA的浓度，在对照条件下以及用浓度递增的秋水仙碱（5、10和50微摩尔）处理的制剂中相似。相比之下，发现细胞松弛素B（5、10和50微摩尔）会使加载L-DOPA（10 - 100微摩尔）的肾切片中多巴胺及其脱氨代谢产物DOPAC的形成呈浓度依赖性降低。发现细胞松弛素B对多巴胺形成的抑制作用在用哇巴因（500微摩尔）预处理的肾切片中或当孵育液中的钠浓度从120毫摩尔降至20毫摩尔时完全消除。单独使用时，发现哇巴因（500微摩尔）可使多巴胺的形成减少55%；将孵育培养基中的钠浓度降低至20毫摩尔的效果也使多巴胺的形成显著减少（降低53%）。DOPAC的积累始终与其母体胺的积累平行。结论是，肾中多巴胺的形成取决于培养基中的钠浓度以及钠的肾小管转运的完整性，即肌动蛋白细胞骨架与Na +,K(+)-ATP酶之间的关联似乎起决定性作用。
